This project involves two goals: (1) Development of simple tests for detection of chemical abnormalities, suitable for the dried spots of blood already collected from newborn infants to screen for phenylketonuria and other inborn errors of metabolism by methods devised by this laboratory. (2) Search for new inborn errors of metabolism among developmentally disabled subjects whose family history suggests an autosomal recessive mode of inheritance of the disorder. Methods used emphasize use of bacterial inhibition assays, bacterial auxotrophs and special mutants, as well as paper, thin-layer, gas and liquid chromatographic procedures. Recent tests developed include those for alpha-l-trypsin inhibitor deficiency, hemoglobin abnormalities and disorders of tryptophane and purine metabolism. Under development are tests for glutathione synthetase deficiency and hypercholesterolemia. Screening of institutionalized mentally retarded patients with familial history suggesting autosomal recessive inheritance has led to detection and study of a second case of "tryptophanuria with dwarfism" and two cases of p-hydroxyphenylacetic aciduria which appear to be due to an inborn error of metabolism, rather than malabsorption of dietary tyrosine.